1. Field of the Invention
The present invention relates to a method and device for measuring blood component concentrations, and more particularly, to a noninvasive method and device for measuring blood component concentrations for components such as glucose, cholesterol, albumin, hemoglobin and bilirubin and some other analytes like alcohol and drugs based on spectroscopy.
2. Description of the Related Art
Previous devices for monitoring blood component concentrations of a patient are known. These devices typically use a small blood sample by pricking the tip of a finger which is placed on a chemically treated carrier and is inserted into a portable instrument to measure blood component concentrations. This finger prick is painful and can be a problem when samples are required often. Moreover, although the cost of these instruments is not significant, the cost for the disposable items (test strips, lancets and so on) and the health risks associated with having an open wound is not desirable. Moreover, the time interval between the moment the blood sample is placed on a chemically treated carrier and the moment the carrier is inserted into an instrument is critical and is a source of inaccuracy. Accordingly, there is a widespread demand for noninvasive determination of glucose for millions of diabetics all over the world. Many of them need several glucose tests each day to provide correct insulin control and diet. Noninvasive bilirubin measurements are useful for newborns with jaundice and cholesterol measurements are useful for people who suffer from arteriosclerosis.
Various schemes have been attempted to measure blood component concentrations in a noninvasive manner. Among them, U.S. Pat. Nos. 4,901,728 and 5,009,230 use an optical activity property of glucose and a rotation angle of the polarization is measured when a polarized light beam passes through a vascularized part of the body. The accuracy of the measurement is limited by small absorption of glucose in the range of 940-1000 nm and the existence of other components with optical activity properties in the human body (for example, some amino acids).
Another technique uses noninvasive sensor systems for glucose monitoring of the aqueous humor of the eye on the basis of polarization as shown by March, U.S. Pat. No. 3,958,560 or Raman spectroscopy (Tarr et al., U.S. Pat. No. 5,243,983). Unfortunately, these techniques may cause considerable discomfort to the patient because of the need to place a device on the patient's eye. A more accurate and less intrusive system is desired.
Another spectroscopic approach is based on near infrared absorption or reflection spectroscopy. Several of the references mentioned above utilize absorption or reflection spectroscopy to measure the glucose concentration in the human blood. The basic principle is to send light of several wavelengths into subcutaneous tissue containing blood and to detect the intensity of the light reflected or transmitted through the tissue. Using well developed mathematical algorithms, it is possible to calculate the glucose concentration from the light intensity values. The near infrared region of the spectrum is suitable for noninvasive measurement of concentrations of blood components because of the relatively good light transmission of skin tissues at these wavelengths. The main disadvantages of this approach are the low concentration of glucose in tissue relative to water that has significant absorption in this region; several other components in tissue interfering with glucose in light absorption; significantly non-homogeneous tissue structure and corresponding non-homogeous distribution of glucose in tissue; light scattering properties of tissue influence on the quantitative light absorption measurements. Thus, the right choice for measurement of spectral range and the rules of wavelength selections are important to provide accuracy in glucose concentration determination.
The spectral range 800-1850 nm is suitable for performing quantitative measurements because in this range, the water absorption line at 1450 nm does not significantly overlap with absorption lines of other components such as protein, fat, hemoglobin, oxy-hemoglobin and at the same time it is possible to select a separate glucose absorption line in the vicinity of 1600 nm.
Constituents absorption in this region is greater than, for example, in the range 600-100 nm which is used in U.S. Pat. No. 5,028,787 and, as a consequence, it is possible to provide the necessary accuracy in glucose determination using a simpler concentration calculation algorithm. On the other hand, in the wavelength selection and corresponding calculation algorithm, the reference wavelength is selected so that the reflectance of the light is substantially unaffected by the concentration of a blood component and a signal wavelength is selected among infrared wavelengths at which the reflectance varies with the concentration of a blood component being measured. Their corresponding electrical signal ratio is not sufficient for accurate determination of blood glucose concentration taking into account blood and tissue components which absorb light in this spectral range. It is necessary to keep in mind a possibility that when other components (not glucose) of blood change their concentration, it will cause a change in the reflectance on the wavelength selected for glucose measurement.
It should be noted that only Braig et al. (U.S. Pat. No. 5,313,941) emphasizes the advantages of pulsed near infrared light source for blood glucose determination. However, Braig et al. uses broadband pulses of infrared light which are emitted in the range of 2-20 .mu.m and are synchronized with the systole and diastole of the patient cardiac cycle. At the same time, it is possible to point out the evident advantages of pulsed polychromatic light source such as a Xe flash lamp. Flash lamp light sources have higher peak power than Light-Emitting Diodes and in comparison with known laser diodes, the main advantage is that a pulsed flash lamp provides a continuous spectrum. As a consequence, selecting any wavelength is possible and, they are not as expensive as laser diodes. Moreover, pulsed flash lamps can be significantly smaller than polychromatic light sources such as quartz-halogen or tungsten-halogen bulb.
Therefore, it is possible to develop compact personal monitoring device based on a pulsed flash lamp. This kind of device was proposed by A. Yamanishi (U.S. Pat. No. 4,267,844) for measurement of bilirubin concentration using a two wavelength algorithm (one wavelength is selected as a signal corresponding to the absorption of bilirubin and the other was selected as a reference signal corresponding to the background absorption). A noninvasive device for cholesterol measurement is also known in U.S. Pat. No. 5,246,004 where the light of a plurality of discrete wavelengths selected from the near infrared spectrum is used to illuminate the blood and the above-mentioned algorithm using the ratio of the signal and a background reference signal is used.
One of the main disadvantages in biomedical applications of near infrared reflectance spectroscopy, as described above, is variations in the spectral baseline. For example, in recent investigations aimed at transcutaneous glucose monitoring, baseline variations in spectra were found to overwhelm the spectral features associated with glucose absorption. The scattering coefficient of biological tissue depends on many structural fibers and the shapes and sizes of cellular structures. To obtain reproducible absorption data from the near infrared reflectance spectroscopy, one must minimize the effects of changes in the scattering background.
Thus, there is a great need for a method and device for noninvasive blood glucose concentration measurement which provide reliable and accurate results.